L-Fucose ameliorates DSS-induced acute colitis via inhibiting macrophage M1 polarization and inhibiting NLRP3 inflammasome and NF-kB activation

Int Immunopharmacol. 2019 Aug:73:379-388. doi: 10.1016/j.intimp.2019.05.013. Epub 2019 May 24.

Abstract

Previous studies reported that L-fucose had anti-inflammatory effects in respiratory and cutaneous system. However, the effect of L-fucose on colitis and the underlying mechanism is poorly understood. We studied the anti-inflammatory effects of L-fucose on Dextran sulfate sodium (DSS)-induced acute colitis in vivo and on LPS/ATP-induced bone marrow derived macrophages (BMDMs) damage in vitro. Our results show that L-fucose significantly alleviated weight loss and disease activity index (DAI) scores in colitis and reduced the infiltration of macrophages and neutrophils. In addition, L-fucose can inhibit macrophage M1 polarization, inactivate the NLRP3 inflammasome and reduce the release of TNFα, IL1β, IL6 pro-inflammatory cytokines. In vitro studies showed that L-fucose ameliorated cell damage resulting from the administration of LPS with ATP in BMDMs, inhibited NLRP3 inflammasome activation and reduced the release of corresponding pro-inflammatory cytokines. Finally, L-fucose can inhibit the expression of p-NF-kB in vivo and in vitro. Overall, our results show that L-fucose can attenuate colitis by inhibiting macrophage M1 polarization, inhibiting NLRP3 inflammasome and NF-kB activation, and down-regulation of pro-inflammatory cytokines.

Keywords: L-Fucose; NF-kB; NLRP3; Ulcerative colitis.

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / immunology
  • Colitis / pathology
  • Colon / drug effects
  • Colon / immunology
  • Colon / pathology
  • Cytokines / genetics
  • Cytokines / immunology
  • Dextran Sulfate
  • Fucose / pharmacology
  • Fucose / therapeutic use*
  • Inflammasomes / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Mice, Inbred C57BL
  • NF-kappa B / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammasomes
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Fucose
  • Dextran Sulfate